X-linked Opitz G/BBB Syndrome: MID1 Gene Deletion/Duplication

Condition Description

X-linked Opitz G/BBBsyndrome is a congenital midline malformation syndrome characterized by facialanomalies, laryngo-tracheo-esophageal defects, and genitourinary abnormalities.Facial anomalies seen in X-linked Opitz G/BBB syndrome include ocularhypertelorism, prominent forehead, widow's peak, broad nasal bridge, andanteverted nares. Genitourinary abnormalities include hypospadias,cryptorchidism, and hypoplastic/bifid scrotum. The condition is geneticallyheterogeneous, as there is an autosomal dominant form as well.

Hypertelorismand hypospadias are the most frequent manifestations of X-linked Opitz G/BBBsyndrome, being present in almost all individuals. Developmental delay andmental retardation are observed in about 50% of affected males. Cleft lip and/or palate are present in approximately 50% of affected individuals. Other malformations present in fewer than 50% of individualsinclude congenital heart defects, imperforate or ectopic anus, and midline brain defects(Dandy-Walker malformation and agenesis or hypoplasia of the corpus callosumand/or cerebellar vermis). Monozygotic twinning is unusually frequent infamilies of individuals with X-linked Opitz G/BBB syndrome, and may be amanifestation of the defect; unusually severe cases with early lethality occuras twins. Wide clinical variability occurs even among members of the samefamily. Female carriers usually manifest only ocular hypertelorism. Theprevalence of X-linked Opitz G/BBB syndrome ranges from one in 50,000 to one in100,000 males.

Thediagnosis of X-linked Opitz G/BBB syndrome is established most often byclinical findings. MID1 (Xp22) is the only gene currently known to be associated with X-linked Opitz G/BBB syndrome. Sequence analysis of the MID1 gene detects mutations in15%-45% of males with clinically diagnosed Opitz G/BBB syndrome. Deletions andduplications in and of the MID1 genehave also been reported. The cohorts tested for MID1 mutations ofteninclude simplex cases (i.e., individuals with no family history of Opitz G/BBB syndrome), who therefore cannot be determined to have either theX-linked form or the autosomal dominant form. The detection rate is higher in individuals with clear X-linkedinheritance. De novo mutations havebeen reported.

Click here for the GeneTests summary on this condition.

Genes (1)

Indications

This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of X-linked Opitz G/BBB syndrome in individuals who have tested negative for sequence analysis
  • Carrier testing in adult females with a family history of X-linked Opitz G/BBB syndrome who have tested negative for sequence analysis

Methodology

DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.

Detection

Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

When sample fails to meet the acceptable criteria, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)
WBP

Requirements
EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 24 hours of collection. Do not refrigerate or freeze.
DNA, Isolated
DNA

Requirements
Microtainer
3µg
Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.
  • Sequencing analysis of the MID1 gene is available (ZC) and is required before deletion/duplication analysis.
  • ACGH array-based test for deletion/duplication analysis of 64 differentX-linked intellectual disability genes is available (OL).
  • Prenataltesting is available to adult females who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.

How to Order